Mitochondrial disorders

Abstract

Mitochondria, the organelles devoted to energy production, have unique genetic features. They possess their own genome encoding several subunits of the respiratory chain, the majority of which are encoded by nuclear DNA, as well as factors involved in replication, transcription and translation of mitochondrial DNA. In the past few years, molecular lesions of mitochondrial DNA have been reported with increasing frequency as a source of human disorders. Several mutations of mitochondrial DNA, either as sporadic large scale rearrangements (deletions, duplications) or maternally-inherited point mutations, have been associated with well defined clinical syndromes. Furthermore, because of the nuclear DNA contribution to the synthesis of respiratory chain enzymes, phenotypes transmitted as Mendelian traits have also been identified and associated with qualitative (multiple deletions) and quantitative (depletion) lesions of the mitochondrial genome. The clinical manifestations of mitochondrial DNA mutations are extremely heterogeneous, ranging from myopathies, encephalomyopathies, cardiopathies, to complex multisystem syndromes. Clinical, morphological, biochemical and molecular genetic data are necessary for diagnosis. The recent advances in genetic studies provide both diagnostic tools and new pathogenetic insights into this rapidly expanding area of human pathology.